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Meta-Analysis
. 2024 May 27;14(1):12094.
doi: 10.1038/s41598-024-61628-9.

HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study

Kang Qu  1 , Ming-Xi Li  1 , Peng Yu  2 ; International Headache Genetics Consortium; Bai-Hua Wu  1 , Miao Shi  1 , Ming Dong  3
Collaborators, Affiliations
Meta-Analysis

HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study

Kang Qu et al. Sci Rep. .

Abstract

Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30-1.84, P = 6.87 × 10-7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

Keywords: HMG-CoA reductase; Mendelian randomization; Migraine; Statins.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Overview of the study design in this study.
Figure 2
Figure 2
Associations linking HMG-CoA reductase gene expression or HMG-CoA reductase mediated low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol with the risk of migraine.
Figure 3
Figure 3
The visualization of HMG-CoA reductase gene expression and the colocalization analysis with migraine.
Figure 4
Figure 4
Meta-analysis of mendelian randomization analysis results based on inverse variance weighting.
Figure 5
Figure 5
Associations between genetically proxied statins lipid-lowering drugs and the risk of coronary artery disease as a positive control analysis.
See this image and copyright information in PMC

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